In Fiscal Year 2021, outsourcing facilities submitted 101 adverse event reports to the FDA’s Center for Drug Evaluation and Research (CDER) Compounding Incidents Program. These reports from outsourcing facilities comprised approximately 33% of all compounding incidents received by FDA during that time.

Outsourcing facilities are required to electronically report all serious and unexpected adverse drug experiences associated with the use of their compounded drug products to FDA within 15 calendar days of first receiving the information. FDA also strongly recommends that outsourcing facilities report all serious adverse drug experiences, expected and unexpected, associated with their compounded drug products to provide important information about potential product quality issues or public health risks associated with drug products compounded by outsourcing facilities or drug components used by the outsourcing facilities to compound the drug products. These reports should be submitted electronically via either FDA’s Safety Reporting Portal (SRP) or via the Electronic Submissions Gateway (ESG). Details are described in the Adverse Event Reporting for Outsourcing Facilities Under Section 503B of the Federal Food, Drug, and Cosmetic Act Guidance for Industry. Failure to report adverse events is a prohibited act and such violations are subject to regulatory and enforcement action.

In addition to receiving adverse event submissions directly from outsourcing facilities, FDA may also receive complaint reports from other sources, such as consumers or healthcare providers, covering a wide range of issues, including product quality issues (such as sub- or super-potency, contamination, particulate matter, or pH issues); insanitary conditions within a facility; compounders making false or misleading claims about their drugs; and compounding of ineligible bulk drug substances, to name a few.

The Compounding Incidents Program utilizes adverse event reports and other complaint reports to identify signals of potential quality problems that may be associated with a particular drug or drug component, and which may have been caused by conditions or processes at a facility where the drug or its components were made or handled. These types of cases are differentiated from medication errors, hospital or clinic procedural problems, or quality issues associated with ingredients such as active pharmaceutical ingredients or excipients.

Each report is evaluated on a case-by-case basis, and FDA may contact the outsourcing facility or the reporter to obtain additional information. The information gathered may assist FDA in determining the appropriate actions such as:

• Inspection to further investigate the reported incident; subsequent regulatory actions may include warning letters, untitled letters, recalls, or other actions.
• Sample collection and testing at FDA laboratories.
• Referral or notification to other FDA centers or offices for appropriate action if an issue spans product areas.
• Notification to and/or a request for information from other government agencies or state regulatory authorities.
• Notification of professional organizations regarding broader compounding-related issues.
• Public communications such as Compounding Risk Alerts; and/or
• Revision or development of policies or guidance documents.

When an outsourcing facility learns of an adverse drug experience associated with their compounded product, it should actively seek to obtain the following four data elements:

• an identifiable patient (to indicate the existence of a specific patient)
• an identifiable reporter (to indicate that the reporter is an identifiable person who claims to have knowledge about the patient, adverse event, and drug involved)
• a suspect drug product (to describe the attributes of the product that the initial reporter suspected was associated with the adverse event)
• a serious adverse event (to indicate the unexpected adverse event to FDA that results in death, a life-threatening adverse drug experience, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, and/or a congenital anomaly or birth defect.)

If the outsourcing facility has information on at least the suspect drug and the adverse event, it should submit a 15-day “Alert report” to FDA as soon as possible (but no later than 15 calendar days after first receiving the information), and also promptly investigate adverse events that are the subject of the report. If the outsourcing facility was not able to include all four of the data elements in the initial report, it should continue to try and obtain the information, along with reporting any new information that could assist FDA with the investigation.

Before submitting an adverse event report in electronic format to FDA for the first time either via the SRP or ESG, the outsourcing facility should notify the FDA Adverse Event Reporting System (FAERS) Electronic Submission Coordinator of its intent at faersesub@fda.hhs.gov. The FAERS Coordinator will assist the outsourcing facility to ensure that all steps have been completed for successful submission of adverse event reports. Details are included in the draft guidance for industry, Providing Submissions in Electronic Format – Postmarketing Safety Reports.

As part of its inspections of outsourcing facilities, FDA may review adverse event information received by the outsourcing facility and may review whether the outsourcing facility has developed and implemented written processes for the surveillance, receipt, evaluation, and reporting of adverse events for the drug products it compounds.

FDA’s Compounding Incidents Program is critical in helping to protect the public against poor quality compounded drugs through surveillance and review of adverse events, product quality reports, and complaints, ultimately supporting FDA’s mission to protect public health. Additional information is available on FDA’s Human Drug Compounding webpage.

Resources

Mitigating Risks of Compounded Drugs Through Surveillance

Adverse Event Reporting for Outsourcing Facilities Under Section 503B of the Federal Food, Drug, and Cosmetic Act Guidance for Industry

Providing Submissions in Electronic Format – Postmarketing Safety Reports

FAERS Electronic Submissions

Information for Outsourcing Facilities